Myocardial perfusion imaging (MPI) provides additional clinical information on children with cardiac disease but will not benefit children with chest pain and normal cardiac studies. This study reviewed all technetium-99 m ((99m)Tc) sestamibi stress MPI studies between 2004 and 2010 performed in association with graded exercise testing (86% with bicycle ergometer, 14% with treadmill). A positive test was defined as a perfusion defect or abnormal ventricular function response. Clinical records were reviewed, including follow-up assessment to determine accuracy of MPI interpretation. False-positive and false-negative rates were recorded. A total of 197 patients (mean age, 13.4 ± 3.6 years, 70% male) underwent 218 MPI studies. Group A had 42 patients (43 studies) with isolated chest pain and normal studies. Of the 43 studies, 39 had negative results, and 4 had false-positive results. Group B had 155 patients (175 studies) with known or suspected cardiac disease, and 39 tests (33 patients) had positive results. Whereas 32 studies were considered true-positive, 7 were false-positive. There was one false-negative test. According to the findings, (99m)Tc sestamibi MPI studies are clinically useful but not perfect tests in the setting of known or suspected cardiac disease based on clinical evaluation, electrocardiography (ECG), or echocardiography. Children who had isolated chest pain with a normal ECG and echocardiogram often have false-positive studies.